Atopic dermatitis (AD) is a common dermatologic condition often associated with significant pruritus. The pruritus and associated scratching can be the most debilitating aspects of AD and exacerbate the dermatitis. Patients often report that current treatments for pruritus in AD are ineffective. An agent that would provide relief of the pruritus associated with AD would be very important in the control of the disease. Recent studies suggest that serotonin has a role in causing pruritus, and that serotonin antagonists may be beneficial in the treatment of pruritus. Serotonin reuptake inhibitors (SSRIs) may also prove to be effective in the treatment of pruritus. The goals of this investigation are to determine if 12 weeks of paroxetine will 1a) diminish the pruritus associated with moderate to severe AD, 1b) diminish AD associated skin severity, 1c) diminish AD-associated impairment of quality of life, 2a) diminish AD- associated potential co-morbid depression and anxiety, 2b) diminish AD- associated specific neuropsychiatric and bodily symptoms related to imbalances in cytokines that are modulated by anti-depressant therapy, 2c) reduce excessive, habitual, or obsessive-compulsive traits of scratching associated with moderate to severe AD. The study will be a double-blind, placebo-controlled, randomized, single-site study of 40-60 adult subjects with moderate-to severe AD. Patients will receive paroxetine or placebo for 12 weeks followed by a two-week dose taper. Efficiency of treatment will be assessed based on the improvement in itching as measured by the pruritus Visual Analog Scale, improvement in the Physician's Global Assessment of skin symptoms, improvement in the Eczema Area and Severity Index, serial photography, improvement in the subject's Quality of Life in Atopic Dermatitis survey, improvement in the Atopic Dermatitis-Inventory Trait for Compulsive, Habitual, and Excessive Scratching survey, improvement in the Structured Clinical Interview for DSM-IV and the Beck's Depression and Speilberger State- Trait Anxiety Inventory scales, and improvement in the Neurotoxicity Rating Scale of neuro-psychiatric and bodily symptoms.